LAUSR

We read the Maastricht VI/Florence consensus report published in GUT with great interest. The report suggested that vonoprazanbased therapy is superior, or not inferior, to conventional proton pump inhibitor (PPI)based triple therapies for Helicobacter pylori eradication. However, the number of randomised controlled trials (RCTs) was small and the majority of previous trials were conducted in Japan. Recently, several new RCTs from other populations have been reported. Therefore, we conducted an updated systematic review and metaanalysis of RCTs to compare the efficacy and tolerability of vonoprazan and PPIbased therapies for H. pylori eradication. Detailed methods of the inclusion and exclusion criteria, systematic review, and statistical methods were shown in online supplemental file 1, and the registration number is CRD42023394825. Of the 489 articles identified, 476 articles were excluded (online supplemental figure 1). A total of 13 RCTs were included which consisted of 11 firstline therapy trials and the other 2 were secondline and thirdline therapy trial, respectively (online supplemental table 1). The regimens, dose and frequency of antibiotics, durations of treatment and eradication rate by intentiontotreat (ITT) and perprotocol (PP) analysis were shown in online supplemental table 2. Metaanalysis of the 13 trials showed that the overall efficacy of vonoprazanbased therapy was superior to PPIbased therapy in H. pylori eradication in both ITT and PP analyses. The risk ratio (RR) was 1.09 (95% CI 1.03 to 1.05, p<0.01) according to ITT analysis and was 1.09 (95% CI 1.04 to 1.14, p<0.01) according to PP analysis (figure 1). In subgroup analysis according to susceptibility of clarithromycin, vonoprazanbased triple therapy was superior to PPIbased triple therapy in patients with clarithromycinresistant strains (figure 1, RR 1.64, 95% CI 1.21 to 2.23, p<0.01). However, no superiority was found in subgroup with clarithromycinsusceptible strains (RR 1.01, 95% CI 0.98 to 1.04, p=0.57) (online supplemental table 3). There were no significant differences in the frequencies of adverse effect in vonoprazanbased or PPIbased therapies (online supplemental table 4 and figure 3). Subgroup analysis showed that the eradication rates of vonoprazanbased triple therapy and PPIbased triple therapy were 74.9% (257/343, 95% CI 70.1% to 79.2%) vs 41.5% (142/342, 95% CI 36.4% to 46.8%), respectively, in patients with clarithromycinresistant strains (p<0.001) and were 92.5% (418/452, 95% CI 89.7% to 94.6%) vs 90.1% (375/416, 95% CI 86.9% to 92.7%) in patients with clarithromycinsusceptible strains (figure 2). We further constructed a Hpnormogram to assess the efficacy of vonprazanbased or PPIbased triple therapy (figure 2). 10 There was no significant publication bias in this metaanalysis (online supplemental figure 2). In summary, this is an updated and comprehensive systematic review and metaanalysis of RCTs comparing the efficacy of vonoprazanbased and PPIbased therapy. We showed that vonoprazanbased therapy was superior to PPIbased therapy for H. pylori eradication, especially in patients with clarithromycinresistant strains. The Hpnormogram revealed that vonoprazanbased clarithromycin triple therapy would be more effective than PPIbased clarithromycin triple therapy in regions with higher clarithromycin resistance. However, there were some limitations of current evidence. First, among the 13 included RCTs, only 1 study was conducted outside Asia. The geographical and racial factors might limit the generalisability of the results to other parts of the world. Second, lower dosage Letter